Large percentage of patients may not be in SCD specialty care, and may face barriers to care. For adults, not having specialty care may be fatal, because specialists may prescribe Hydroxyurea (HU), the first and only FDA approved remittive drug for SCD. Additional barriers to HU include physician fears or misconceptions about its use, inconsistent determination of HU eligibility and inconsistent dose escalation, and patient failure to take HU, due to ignorance or mistrust of relative benefit sand harms, inconvenience associated with therapy, or poor medication access. To overcome these barriers, the state of Virginia, including the Virginia Department of Health and two academic medical centers, plans a two phase demonstration, first of improvement in the percentage of adults with SCD who are in SCD specialty care (PhaseI), then of improvement in adherence to HU of eligible SCD adults (PhaseII). Both phases will use existing academic SCD providers, and an innovative, multimodal strategy, featuring specially trained SCD patient navigators (PNs), that addresses barriers to care and to HU use. In Phase I we will demonstrate the feasibility of utilizing PNs to overcome patient access barriers to SCD care. In Phase II we will test the efficacy of PNs for overcoming barriers to acceptance of and adherence with Hu therapy. Patients will be randomized to a PN or usual care arm. Providers will implement NIH guidelines for HU eligibility and prescribing in both arms. The primary outcome variable for Phase I will be the percentage of enrollees who in the subsequent three months achieve a visit with a specialty SCD provider. The primary outcome for Phase II will be improvement in the HbF level at 1 year post randomization. Secondary outcomes will include: four measures of adherence to HU; percent of patients achieving either maximum tolerated dose, a clinical endpoint, or maximum dose; ED and hospital visits; mean corpuscular volume; total hemoglobin; white blood cell count; reticulocyte count; and quality of life. Co variates in PhaseII will include: patient demographics; genotype; social support; SCD associated pain conditions; mental health status and alcohol use; and coping measures. This project will be critically important and impactful by demonstrating the feasibility of a statewide community based strategy to assist vulnerable SCD adults in obtaining SCD specialty care and likely prolonging life, a model that other states could adopt. PUBLIC HEALTH RELEVANCE: To overcome barriers to hydroxyurea (HU) among adults with sickle cell disease (SCD), the state of Virginia, including the Virginia Department of Health and two academic medical centers, plans a two- phase demonstration, first of improvement in the percentage of adults with SCD who are in SCD specialty care (Phase I), then of improvement in adherence to HU of eligible SCD adults (Phase II). This project will be critically important and impactful by demonstrating the feasibility of a statewide community-based strategy to assist vulnerable SCD adults in obtaining SCD specialty care and likely prolonging life, a model that other states could adopt.